H
Huw D. Lewis
Researcher at GlaxoSmithKline
Publications - 16
Citations - 897
Huw D. Lewis is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Epigenetics & Colitis. The author has an hindex of 9, co-authored 16 publications receiving 672 citations. Previous affiliations of Huw D. Lewis include University of Hertfordshire.
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Journal ArticleDOI
Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation
Huw D. Lewis,John Liddle,Jim E Coote,Stephen John Atkinson,Michael David Barker,Benjamin D. Bax,Kevin L. Bicker,Ryan P. Bingham,Matthew Campbell,Yu Hua Chen,Chun-wa Chung,Peter D. Craggs,Robert P. Davis,Dirk Eberhard,Gerard Joberty,Kenneth E Lind,Kelly Locke,Claire Maller,Kimberly Martinod,Chris Patten,Oxana Polyakova,Cecil E Rise,Martin Rüdiger,Robert J. Sheppard,Daniel J. Slade,Pamela Thomas,Jim Thorpe,Gang Yao,Gerard Drewes,Denisa D. Wagner,Paul R. Thompson,Rab K. Prinjha,David Matthew Wilson +32 more
TL;DR: Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD3 enzyme have been validated, for the first time, in both histone citrullination and neutrophil extracellular trap formation, validating the critical enzymatic role of human and mouse PAD 4.
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Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design.
Daniel J. Slade,Pengfei Fang,Christina J. Dreyton,Christina J. Dreyton,Ying Zhang,Jakob Fuhrmann,Don L. Rempel,Benjamin D. Bax,Scott A. Coonrod,Huw D. Lewis,Min Guo,Michael L. Gross,Paul R. Thompson,Paul R. Thompson +13 more
TL;DR: These structures identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism that will aid the development of allosteric inhibitors targeting the PADs.
Journal ArticleDOI
Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis.
Van C. Willis,Nirmal K. Banda,Kristen N. Cordova,Piyanka E Chandra,William H. Robinson,D C Cooper,Dave Lugo,Gaurav Mehta,Simon Taylor,Paul P. Tak,Rab K. Prinjha,Huw D. Lewis,V M Holers +12 more
TL;DR: These data extend the previous demonstration of efficacy with the pan‐PAD inhibitor Cl‐amidine and demonstrate robustly that PAD4 inhibition alone is sufficient to block murine arthritis clinical and histopathological end‐points.
Journal ArticleDOI
Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.
John Liddle,Francis Louis Atkinson,Michael David Barker,Paul S. Carter,Neil R. Curtis,Robert P. Davis,Clement Douault,Marion C. Dickson,Dorothy Elwes,Neil Stuart Garton,Matthew Gray,Thomas George Christopher Hayhow,Clare I. Hobbs,Emma J. Jones,Stuart G. Leach,Karen Leavens,Huw D. Lewis,Scott McCleary,Margarete Neu,Vipulkumar Kantibhai Patel,Alex Preston,Cesar Ramirez-Molina,Tracy Jane Shipley,Philip Alan Skone,Nick Smithers,Donald O. Somers,Ann Louise Walker,Robert J. Watson,Gordon G. Weingarten +28 more
TL;DR: The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described, with GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.
Journal ArticleDOI
Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice
Josefa M. Sullivan,Ana Badimon,Uwe Schaefer,Pinar Ayata,James Gray,Chun-wa Chung,Melanie J. von Schimmelmann,Fan Zhang,Neil Stuart Garton,Nicholas Smithers,Huw D. Lewis,Alexander Tarakhovsky,Rab K. Prinjha,Anne Schaefer +13 more
TL;DR: A key role of the BET-controlled gene networks in the development of ASD is suggested, as pharmacological suppression of BET proteins by a highly selective brain-permeable inhibitor results in the suppression of genes that have been linked to autism spectrum disorders in humans.